An article describes Notched T Waves on Holter Recordings Enhance Detection of Patients With LQT2 (HERG) Mutations J. M. Lupoglazoff, MD; I. Denjoy, MD; M. Berthet; N. Neyroud, PhD; L. Demay; P. Richard, PhD; B. Hainque, PhD; G. Vaksmann, MD; D. Klug, MD; A. Leenhardt, MD; G. Maillard, MD; P. Coumel, MD; P. Guicheney, PhD
The 2 genes KCNQ1 (LQT1) and HERG (LQT2), encoding cardiac potassium channels, are the most common cause of the dominant long-QT syndrome (LQTS). In addition to QT-interval prolongation, notched T waves have been proposed as a phenotypic marker of LQTS patients. The T-wave morphology of carriers of mutations in KCNQ1 (n5133) or HERG (n557) and of 100 control subjects was analysed from Holter ECG recordings. Averaged T-wave templates were obtained at different cycle lengths, and potential notched T waves were classified as grade 1 (G1) in case of a bulge at or below the horizontal, whatever the amplitude, and as grade 2 (G2) in case of a protuberance above the horizontal. The highest grade obtained from a template defined the notch category of the subject. T-wave morphology was normal in the majority of LQT1 and control subjects compared with LQT2 (92%, 96%, and 19%, respectively, P, 0.001). G1 notches were relatively more frequent in LQT2 (18% versus 8% [LQT1] and 4% [control], P, 0.01), and G2 notches were seen exclusively in LQT2 (63%). Predictors for G2 were young age, missense mutations, and core domain mutations in HERG. This study provides novel evidence that Holter recording analysis is superior to the 12-lead ECG in detecting G1 and G2 T-wave notches. These repolarization abnormalities are more indicative of LQT2 versus LQT1, with G2 notches being most specific and often reflecting HERG core domain missense mutations. (Circulation. 2001; 103:1095-1101.)
Further is described Quantitative Analysis of T Wave Abnormalities and Their Prognostic Implications in the Idiopathic Long QT Syndrome GABRIELLA MALFATTO, MD,*t GABRIELLA BERIA, MD,*$ SERGIO SALA, MD,*t OSCAR BONAZZI, MD,* PETER J. SCHWARTZ, MD, FACC*§ Milan and Pavia, Italy.
We evaluated the diagnostic and prognostic value of morphologic abnormalities of the T wave (mainly notched or biphasic T waves) in patients affected by the idiopathic long QT syndrome. In the long QT syndrome, these abnormalities in T wave morphology are often observed and are of uncertain significance. The T wave abnormalities in the electrocardiogram (ECG) of 53 patients with the long QT syndrome and 53 control subjects of similar age and gender were analyzed, and their association with major cardiac events was defined. Notched or biphasic T waves were defined according to morphologic criteria. They were present in 33 (62%) of 53 patients with the long QT syndrome and in 8 (15%) of 53 control subjects (p<0.001). Moreover, among patients with the long QT syndrome they were much more frequent in symptomatic (history of syncope or cardiac arrest) than in asymptomatic subjects (30 [81%] of 37 vs. 3[19%] of 16, p<0.001). The same distribution was observed within families with the long QT syndrome, in which symptomatic members had more pronounced T wave abnormalities than did their asymptomatic siblings or parents. In symptomatic patients, the occurrence of T wave abnormalities was independent of the length of repolarization (corrected QT). These 'I wave abnormalities were associated with the presence of a specific pattern of abnormal left ventricular wall motion. This study has quantified an ECG pattern typical of the long QT syndrome and provides the first evidence that morphologic analysis of T wave abnormalities may contribute to the diagnosis of the long QT syndrome and the identification on patients at higher risk for syncope or cardiac arrest.
Further, an article entitled “T-wave “Humps” as a Potential Electrocardiographic Marker on the Long QT Syndrome” by MICHAEL H. LEHMANN, MD, FACC, FU-MIO SUZUKI, MD, BARBARA S. FROMM, MA, DEBRA FRANKOVICH, RN, PAUL ELKO, PhD, * RUSSEL T. STEINMAN, MD, FACC, JULIE FRESARD, RN, † JOHN J. BAGA, MD, R. THOMAS TAGGART PhD* is described.
This article describes a study attempted to determine the prevalence and electrocardiographic ECG lead distribution on T wave humps (T2 after an initial T wave peak, T1) among families with long QT syndrome and control subjects. T wave abnormalities have been suggested as another facet of familial long QT syndrome in addition to prolongation of the rate corrected QT interval (QTc) that might aid in the diagnosis of affected subjects. The ECG from 254 members of thirteen families with long QT syndrome (each with two or four generations of affected members) and from 2948 healthy control subjects (8≧16 years QTC intervals of 0.39 to 0.46 s) were collected and analysed. T2 was present in 53%, 27% and 5% of blood relatives with a prolonged QCT interval. These findings are consistent with hypothesis that in families with long QT syndrome, T wave humps involving left precordial or especially limps leads, even among asymptotic blood relatives with borderline QCT interval, suggested the presence of the long QT syndrome trait.
An article concerns Fractionated Repolarization Induced by Sotalol in Healthy Subjects M Vaglio, J P Couderc, X Xia, W Zareba Heart Research Follow-up-Program University of Rochester Medical Center, Rochester N.Y., USA.
Over the past five years, regulatory authorities have been increasingly concerned with QT prolongations induced by non-cardiac drug and have recommended pharmaceutical companies to include a careful assessment of the QT interval in their drug development programs. There are controversies around the predictive value of QT prolongation in safety-drug assessment studies. The prolongation of the QT interval is an imperfect, but accepted, surrogate marker of drug cardiac toxicity. In this study, we hypothesize that the inhomogeneous effect of QT prolonging drug in the different layers of the myocardium would not only delay cardiac repolarization, but also perturb the repolarization wavefront on surface ECGs. Principal component analysis (PCA) was applied to the L2-lead ECG Holter recordings. The first two eigenvectors (eu1, eu) were computed. From PCA, several parameters were calculated based on the first eigerwector and on the T-loop. We demonstrated slower repolarization and perturbed T-wave front; 30 min after sotalol administration, turbulence of repolarization velocity increased by 9.02%, p<0.05, occurring prior to QT prolongation. These abnormalities were mainly located in the ascending part of the T-wave, where as the descending part seemed to be less affected at this early phase. In conclusion, analyzing repolarization morphology might help identifying early drug-induced repolarization changes, which could be missed when relying exclusively on QT measurements.
The four mentioned articles all concern manual detection of ECG curvatures. Hundreds of curves have to be analysed manually in order to read the results mentioned in these articles. The manual method is effective for determination for a single patient, but only highly educated medical specialists are able to analyse the curvature. When such a judgement of ECG curvatures is only for specialists, they have to spend several hours per day just to analyse ECG curvatures. An open question is how effective even highly trained specialists are after having analysed curvatures for hours. There is always the risk that they overlook small deviations in the curvature. Due to a computerised curvature, analysis is much more effective, and a much higher number of curvatures can be analysed in a rather short period. There is not any risk that the computer system will overlook deviations in the curvature. A computerised system can make an effective selection between patients with deviations in the curvature and healthy people with a normal curvature.
EP 1 543 770 concerns a system or a method for analysing ECG curvature where at least one among a number of different parameters is isolated, which system has an input means connected to an ECG source, where the different parameters of a received ECG curvature are indicated and/or isolated and for indicating possible symptoms which relate to or are indications of certain deceases, where said deceases are known to influence the ECG curvature. First number of selected parameters are combined in at least a first mathematical analysis, where the result of the analysis can be represented as a point in a coordinate system comprising at least two axes where the system can compare the actual placement in the coordinate system with a number of reference parameters stored in the system for indicating diseases having influence on the ECG curvature. Hereby, it is achieved that any symptom of a disease having an indication (influence) in the ECG curvature can be detected in an objective and automated way.
WO 2005/058156 concerns a system or a method for analysing drug influence on ECG curvature and Long QT Syndrome where at least one among a number of different parameters is isolated, which system has a input means connected to an ECG source, where the different parameters of a received ECG curvature are indicated and/or isolated and for indicating possible symptoms which relates to or are indications of certain diseases, where said diseases are known to influence the ECG curvature. The aim of the invention is to achieve a system and a method for diagnosing Long QT Syndrome in an objective, fast and effective way by indication of a number of symptoms derivable from an ECG curve. Further aim of the invention is to achieve an effective test of drug influence on ECG curvature. This can be achieved with the system previously described if a first number of selected parameters is combined in at least a first mathematical analysis, where the result of the analysis can be represented as a point in a coordinate system comprising at least one axis where the system can compare the actual placement in the coordinate system with a number of reference parameters stored in the system for indicating symptoms or diseases having influence on the ECG curvature, where the system analyses the QT curvature of the ECG curvature for indicating Long QT syndrome. Hereby, it is achieved that any symptom of hereditary or acquired Long QT Syndrome having an indication (influence) in the ECG curvature can be detected in an objective, automated and very fast way.
US 2005/0234357 concern a method and apparatus for detecting cardiac repolarization abnormality using at least one electrocardiogram signal. The at least one electrocardiogram signal can be obtained from any number of continuous or non-continuous windows. The method can include deriving a total quantity of representative beats of the at least one electrocardiogram signal. At least one morphology shape descriptor can be used to determine a total quantity of values representing the total quantity of representative beats. Data corresponding to at least some of the total quantity of values can be used to assess cardiac repolarization abnormality.
U.S. Pat. No. 7,072,708 concerns a method in a computer system for detecting myocardial infarction including the steps of (a) receiving ECG data, (b) analyzing that data for the presence of benign ST data, and (c), when the ST data is not benign, (1) establishing a pathological threshold, (2) normalizing any deviation in the ECG data, (3) applying a pattern analysis to the normalized ECG data, and (4) generating a score indicating the presence of a myocardial infarction based on the pattern analysis and the threshold.
WO 2005/00269 concern implantable cardiac rhythm management device e.g. pacemaker, determines fundamental frequency of sampled signal by autocorrelating function of series of characteristic points each having time of lobe in curvature series. This can be achieved by estimating a frequency of a sampled cardiac rhythm signal and classifying the rhythm. The received signal is sampled and transformed into a curvature series. A lobe in the curvature series corresponds to a characteristic point in the sampled series. Characteristic points are selected based on a time of a lobe in the curvature series and, in one embodiment, amplitude of the signal at the time of the lobe. A frequency of the sampled series is estimated by autocorrelating a function of the series of the characteristic points. In one embodiment, the function is a time difference function. The rhythm is classified by plotting the timewise proximity of characteristic points derived from an atrial signal with characteristic points derived from a ventricular signal. Regions of the plot are associated with a particular rhythm and the grouping of the data corresponds to the classification.